Lipoprotein(a) (Lp(a)) is a low-density lipoprotein-like particle formed by the association of apolipoprotein(a) (Apo(a)) with apolipoprotein B100 (ApoB100). The Apo(a) component is covalently linked to the ApoB100 component in the assembled Lp(a) particle via a disulfide bond. Elevated serum Lp(a) has been shown in several studies to correlate with a variety of atherosclerotic and thrombotic disorders. (See, e.g., Marcovina and Koschinsky (1998), Am. J. Cardiol. 82:57U-66U; Ignatescu et al. (1998), Thromb. Haemost. 80:231-232; Lippi and Guidi (2000), Q. J. Med. 93:75-84; Bennet et al. (2008), Arch. Intern. Med. 168:598-608; The Emerging Risk Factors Collaboration (2009), J. Am. Med. Assoc. 302:412-423; and Lamon-Fava et al, (2011), J. Lipid Res. 52:1181-1187). Thus, therapeutic reduction of serum Lp(a) levels has been suggested as a means for treating or reducing the risk of cardiovascular disorders. There are few available therapeutic options for lowering serum Lp(a) levels. Examples of treatments that have been tested and/or proposed for lowering serum Lp(a) include administration of acetylsalicylic acid, L-carnitine, niacin or anacetrapib, or LDL apheresis. (See, e.g., Parhofer (2011), Curr. Pharm Des 17:871-876). No currently available treatments, however, provide adequate and practical therapy for elevated Lp(a).
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a proprotein convertase belonging to the proteinase K subfamily of the secretory subtilase family. The use of PCSK9 inhibitors (anti-PCSK9 antibodies) to reduce serum total cholesterol, LDL cholesterol and serum triglycerides is described in US Patent Appl. Publ. No. 2010/0166768. Nonetheless, heretofore, PCSK9 inhibitors have not been shown to lower Lp(a) levels in patients. Thus, there remains a need in the art for therapeutic methods of lowering serum Lp(a) levels.